To date, research involving Chlamydia and its host interactions has been hampered by the lack of a functional genetic transformation system. The recently available sequence of the Chlamydia trachomatis genome allows a comprehensive approach in studying this organism. C. trachomatis is an important human pathogen responsible for sexually transmitted disease throughout the world. Current research suggests that chlamydial infections are immunologically mediated. The sequelae of these infections results from a persistent in vivo state where the chlamydial cycle is arrested, while antigen remains a stimulus to the immune response. Many of these infections persist unrecognized for months to years. The biological state of Chlamydia and the factors that lead these persistent infections are unknown. This proposal addresses the study of transcriptional regulation during the chlamydial developmental cycle using a global genomic approach and the determination of whether Chlamydia regulate their developmental cycle to promote persistent infections. These experiments will aid in the elucidation of the molecular mechanisms behind chlamydial persistent infections in order to provide new therapeutic approaches to prevent and treat infections caused by this organism.